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Role of selenoprotein M knockdown in the melatonin antagonism of nickel-induced apoptosis and endoplasmic reticulum stress in mouse heart

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2023年第5期24卷 406-417页

作者： Xintong ZHANG Xiaoxue GAI lihua xu Wenxue MA Qiaohan LIU Bendong SHI Cheng FANG Jingzeng CAI Ziwei ZHANG College of Veterinary Medicine Northeast Agricultural UniversityHarbin 150030China Suihua Agricultural and Rural Bureau Suihua 152000China College of Veterinary Medicine Northeast Agricultural UniversityHarbin 150030China4.Key Laboratory of the Provincial EducationDepartment of Heilongjiang for Common Animal Disease Prevention and TreatmentNortheast Agricultural UniversityHarbin 150030China

The aim of this study was to investigate the role of selenoprotein M(SelM)in endoplasmic reticulum stress and apoptosis in nickel-exposed mouse hearts and to explore the detoxifying effects of melatonin.At 21 d after intraperitoneal injection of nickel chloride(NiCl_(2))and/or melatonin into male wild-type(WT)and SelM knockout(KO)C57BL/6J mice,NiCl_(2)was found to induce changes in the microstructure and ultrastructure of the hearts of both WT and SelM KO mice,which were caused by oxidative stress,endoplasmic reticulum stress,and apoptosis,as evidenced by decreases in malondialdehyde(MDA)content and total antioxidant capacity(T-AOC)activity.Changes in the messenger RNA(mRNA)and protein expression of genes related to endoplasmic reticulum stress(activating transcription factor 4(ATF4),inositol-requiring protein 1(IRE1),c-Jun N-terminal kinase(JNK),and C/EBP homologous protein(CHOP))and apoptosis(B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),Caspase-3,Caspase-9,and Caspase-12)were also observed.Notably,the observed damage was worse in SelM KO mice.Furthermore,melatonin alleviated the heart injury caused by NiCl_(2)in WT mice but could not exert a good protective effect in the heart of SelM KO mice.Overall,the findings suggested that the antioxidant capacity of SelM,as well as its modulation of endoplasmic reticulum stress and apoptosis,plays important roles in nickel-induced heart injury.

关键词： Selenoprotein M(SelM) Nickel chloride(NiCl_(2)) Melatonin Apoptosis Mouse heart

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Altered attentive bias towards interpersonal communication information across phases of schizophrenia: an eye-tracking study

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General Psychiatry 2022年第2期35卷 119-126页

作者： Yikang Zhu lihua xu Qian Guo Tianhong Zhang Xiaochen Hu Paul Enck Jijun Wang Chunbo Li Shanghai Key Laboratory of Psychotic Disorder Shangai Mental Heath CenterShanghai Jiao Tong University School of MedicineShanghaiChina Department of Psychiatry and Psychotherapy Medical FacultyUniversity of ColognenCologneGermany Department of Interal Medicine VI:Psychosomatic Medicine and Psychotherapy University Hospital TubingenTubingenGermany CAS Center for Excellence in Brain Science and Intelligence Technology(CEBSIT)Chinese Academy of Sciences ShanghaiChina Institute of Psychology and Behavioral Science Shanghai Jiao Tong UniversityShanghaiChina

Background Eye movement abnormality in schizophrenia has been studied for several decades.However,patient differences in eye movements across phases of schizophrenia from eye-tracking studies have not been well documented.Aims This pilot study used eye-tracking technology to investigate attentive bias towards interpersonal communication information across different clinical phases of schizophrenia.Methods This study included 78 persons at clinical high risk(CHR)for schizophrenia,68 first-episode(FEZ)patients,and 39 chronically ill patients from the Shanghai At Risk for Psychosis Extending Project(SHARP Extending cohort)as well as 74 healthy controls(HCs).The experiment was an unguided-viewing task composed of 24 trials showing three types of pictures which varied in the degree of interpersonal communication.Type 1 was a scenery picture without people,type 2 was a picture with four people not communicating,and type 3 was a picture with four people communicating.We used two measures:(1)initial fixation duration and(2)total fixation duration.Results A ratio for both measures was calculated between measures for pictures with more or less interpersonal communication.The ratio of initial fixation duration for pictures with people communicating versus pictures with people not communicating was lowest in chronically ill patients(0.13(0.34))compared with HCs(0.31(0.36)),FEZ patients(0.31(0.46)),and CHR patients(0.36(0.42)).The difference in the ratios of initial fixation duration for type 2 and type 3 pictures was also significant for female participants(HCs vs chronically ill patients,t=2.706,p=0.009;CHR patients vs chronically ill patients,t=4.079,p<0.001).In addition,the ratio of initial fixation duration on pictures with people not communicating versus pictures without people negatively correlated with participants’high-risk symptoms(r=−0.35,p=0.002)among the CHR group and also correlated with the negative symptom subscore on the Positive and Negative Syndrome Scale(PANSS)among chronically ill patients(r=−0.33,p=0.037

关键词： schizophrenia communication measures

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Reduced temporal activation during a verbal fluency test in clinical high risk of psychosis: a functional near-infrared spectroscopy-based study

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General Psychiatry 2022年第2期35卷 101-108页

作者： Yanyan Wei Xiaochen Tang Tingyu Zhang Wenjun Su lihua xu Huiru Cui Zhenying Qian Tianhong Zhang Jijun Wang EEG and Neuroimaging Department Shanghai Mental Heath Center Shanghai Jiao Tong University School of MedicineShanghaiChina The Seventh Affiliated Hospital Sun Yat-sen University ShenzhenChina Shanghai Key Laboratory of Psychotic Disorders Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina CAS Center for Excellence in Brain Science and Intelligence Technology(CEBSIT) Chinese Academy of ScienceShanghaiChina Institute of Psychology and Behavioral Science ShanghaiJiao Tong UniversityShanghaiChina

Background Clinical high risk(CHR)of psychosis is a state in which positive symptoms cause the subjects distress but do not approach a severity level that fulfils the criteria for a psychotic episode.CHR exhibits cognitive deficits;however,the underlying neurobiological mechanisms remain unclear.This study aimed to investigate whether brain activation measured by the levels of oxygenated hemoglobin(oxy-Hb)in CHR subjects could be correlated with cognitive deficits.Methods Fifty-eight CHR individuals who fulfilled the criteria for attenuated positive syndrome as specified in the Structured Interview for Prodromal Syndrome(SIPS)and the Scale of Prodromal Syndrome(SOPS)and 58 age-and sex-matched healthy participants were included in the study.All subjects completed the Measurement and Treatment Research to Improve Cognition in Schizophrenia(MATRICS)Consensus Cognitive Battery(MCCB)that includes tests measuring attention,verbal memory,verbal fluency,executive function,and general intelligence.Functional near-infrared spectroscopy(fNIRS)was used to measure the level of oxy-Hb in the dorsolateral prefrontal and frontotemporal cortices.Results We observed significantly decreased oxy-Hb levels in channel 32(located in the right superior temporal gyrus,rSTG)within the CHR individuals compared with that in the healthy controls(HCs)(t=−3.44,Bonferroni-corrected p=0.002),indicating lower brain activity.A significant positive correlation was observed between task-relatedβvalues and working memory in the CHR group(r=0.35,p=0.008).Conclusions The brain activation of rSTG is abnormal among subjects at clinicial high risk for psychosis.This abnormality is probably associated with the neural mechanisms of deficits in the working memory during the early stage of psychosis.

关键词： distress activation verbal

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Spatial sight analysis of Hangzhou Xiaoyingzhou based on tourists’landscape preference

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Frontiers of Architectural Research 2023年第6期12卷 1157-1170页

作者： Yiying Chen Qiwei Ma lihua xu Yijun Shi Zhangwei Lu Yaqi Wu Mao Feng College of Landscape Architecture and Architecture Zhejiang Agriculture and Forestry UniversityHangzhou 310000China

Tourist preferences are important for the high-quality planning and design of recreation spaces.The famous scenic locale of West Lake in Hangzhou,China,is used as an example in this study.Based on multi-source data(e.g.,online comments,and tourist photographs),we used content analysis,kernel density estimation,and image semantic segmentation technology to determine the spatial distribution of tourists’landscape preferences.We analyzed these spatial sight characteristics from the viewpoint,sight distance,and perspectives.The results show that tourists’landscape preferences are mainly concentrated on landscape architecture for recreation.The viewpoints of these preferences are concentrated in the north-south embankmentdfar beyond that of the east-west embankment.The preferences also show a spatial sequence in terms of sight distance,and the best visual effect is the open platform at the north and south islands of Xiaoyingzhou.From the perspective of vision,the degree of spatial openness in the tourists’landscape preferences is proportional to the distance of vision;the two factors have a convergent relationship.The discussion of the characteristics of tourists’landscape preference and space sight creation in Xiaoyingzhou provides a reference for the quality improvement of island recreation space.

关键词： Landscape preference Photo content analysis Landscape Xiaoyingzhou Line of sight analysis

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Different patterns of association between white matter microstructure and plasma unsaturated fatty acids in those with high risk for psychosis and healthy participants

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General Psychiatry 2022年第2期35卷 109-118页

作者： Wenjun Su Zhixing Li lihua xu Jiahui Zeng Yingying Tang Xiaochen Tang Yanyan Wei Qian Guo Tianhong Zhang Jijun Wang Shanghai Key Laboratory of Psychotic Disorders Shanghai Mental Heaith Center Shanghai Jiao Tong University School of MedicineShanghaiChina CAS Center for Excellence in Brain Science and Intelligence Technology(CEBSIT) Chinese Academy of ScienceShanghaiChina Institute of Psychology and Behavioral Science Shanghai Jiao Tong UniversityShanghaiChina

Background Disrupted white matter(WM)microstructure has been commonly identified in youth at clinical high risk(CHR)for psychosis.Several lines of evidence suggest that fatty acids,especially unsaturated fatty acids(UFAs),might play a crucial role in the WM pathology of early onset psychosis.However,evidence linking UFA and WM microstructure in CHR is quite sparse.Aims We investigated the relationship between the plasma UFA level and WM microstructure in CHR participants and healthy controls(HC).Methods Plasma fatty acids were assessed and diffusion tensor imaging(DTI)data were performed with tract-based spatial statistics(TBSS)analysis for 66 individuals at CHR for psychosis and 70 HC.Results Both the global and regional diffusion measures showed significant between-group differences,with decreased fractional anisotropy(FA)but increased mean diffusivity(MD)and radial diffusivity(RD)found in the CHR group compared with the HC group.On top of that,we found that in the HC group,plasma arachidic acid showed obvious trend-level associations with higher global FA,lower global MD and lower global RD,which regionally spread over the corpus callosum,right anterior and superior corona radiata,bilateral anterior and posterior limb of the internal capsule,and bilateral superior longitudinal fasciculus.However,there were no associations between global WM measures and any UFA in the CHR group.Conversely,we even found negative associations between arachidic acid levels and regional FA values in the right superior longitudinal fasciculus and right retrolenticular part of the internal capsule in the CHR group.Conclusions Compared with the HC group,CHR subjects exhibited a different pattern of association between WM microstructure and plasma UFA,with a neuroprotective effect found in the HC group but not in the CHR group.Such discrepancy could be due to the excessively upregulated UFAs accumulated in the plasma of the CHR group,highlighting the role of balanced plasma-membrane fatty acids homeostasis in WM development.

关键词： unsaturated diffusion linking

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Preparation and pharmacokinetics in vivo of linarin solid dispersion and liposome

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Chinese Herbal Medicines 2022年第2期14卷 310-316页

作者： Yingying Huang lihua xu Fangping Zhang Yang Liu Yunyu Wang Fangfeng Meng Shuang Li Xintao Cheng Yuefeng Bi School of Pharmaceutical Sciences Zhengzhou UniversityZhengzhou 450001China Collaborative Innovation Center of New Drug Research and Safety Evaluation Zhengzhou 450001China

Objective:The current investigation aimed to determine the appropriate dosage form by comparing solid dispersion and liposome to achieve the purpose of improving the solubility and bioavailability of linarin.Methods:Linarin solid dispersion(LSD)and linarin liposome(LL)were developed via the solvent method and the thin film hydration method respectively.The Transwell chamber model of Caco-2 cells was established to evaluate the absorption of drug.The pharmacokinetics of linarin,LSD and LL in rats after ig administration were carried out by high performance liquid chromatography(HPLC)method.Results:The solubility of LSD and LL was severally 3.29 times and 3.09 times than that of linarin.The permeation coefficients of LSD and LL were greater than 10^(-6),indicating that the absorption of LSD and LL were both better than linarin.The bioavailability of the LSD was 3.363 times higher than that of linarin,and the bioavailability of LL was 0.9886 times higher than that of linarin.Conclusion:The linarin was more suitable for making solid dispersion to enhance its solubility and bioavailability.

关键词： bioavailability intestinal absorption linarin liposome pharmacokinetics solid dispersion

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Attenuated niacin-induced skin flush response in individuals with clinical high risk for psychosis

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General Psychiatry 2022年第2期35卷 92-100页

作者： Ranpiao Gan Yanyan Wei Guisen Wu Jiahui Zeng Yegang Hu lihua xu Xiaochen Tang Xiaohua Liu Haichun Liu Tao Chen Jijun Wang Tianhong Zhang Shanghai Intelligent Psychological Evaluation and Intervention Engineering Technology Research Center Shanghai Key Laboratory of Psychotic DisordersShanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina Department of Automation Shanghai Jiao Tong UniversityShanghaiChina Big Data Research Lab University of WaterlooWaterlooOntarioCanada Center for Excellence in Brain Science and Itelligence Technology(CEBSIT) Chinese Academy of ScienceShanghaiChina Brain Science and Technology Research Center Shanghai Jiao Tong UniversityShanghaiChina

Background Im paired sesitwity of he soin Mlush response bo miacin is one of the most rpicated findngs in patents with schizoprenia Howewer.prior studies have usaly focused on postonset psychusis,and ll is knowm about the dinical high-risk(CHR)phase of niacin senstity in psychosis Aims To proftle and compare the miacin flush responsge among CHR individuals(converters and non-coverters)patients with frstepso schinophrenia(FES)and healty controls(HCs).Methods Sensivily 1o ftour concentralions (0.1-0001M)of aqueous methylnicotinate was tested in 105 CHR individuals,57 patients with FES and 52 HCs.CHR individuals were further grouped as converters and non converters according to the 2-year follow-up outcomes.Skin flush response scores were rated on a 4-point scale.Results Of the 105 CHR individuals,21 individuals were lost during the study,leaving 84 CHR individuals;16(19.0%)converted to full psychosis at 2 years of fllow-up.Flush response scores identifed in the CHR samples were characterised as modest degree levels,intermediate between those of HC individuals and patients with FES.The flush responses in the CHR group mimicked the responses observed in the FES group at higher concentrations(0.01 M,0.1 M)and longer time points(15 min,20min);however,these became comparable vith the responses in the HC group at the shorter time points and at lower concentr ations.The converters exhibited lower mean flush response scores than the non-converters.Conclusions Attenuated niacin-induced flushing emerged during the early phase of psychosis.New devices should be developed and verified for objective quantification of skin responses in the CHR population.

关键词： Skin high shorter

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含粗骨料超高性能混凝土的单轴受拉力学性能

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建筑材料学报 2024年第2期27卷 167-173页

作者：李力剑刘素梅徐凡丁徐礼华武汉大学土木建筑工程学院湖北武汉430072 江汉大学精细爆破国家重点实验室湖北武汉430056

考虑粗骨料掺量、钢纤维掺量及长径比等因素,研究了含粗骨料超高性能混凝土(UHPC-CA)的单轴受拉力学性能,揭示了纤维增强的机理和粗骨料的作用机制.结果表明:随着粗骨料掺量的增加,UHPC-CA的单轴抗拉强度与变形性能均下降;钢纤维掺量增... 详细信息

考虑粗骨料掺量、钢纤维掺量及长径比等因素,研究了含粗骨料超高性能混凝土(UHPC-CA)的单轴受拉力学性能,揭示了纤维增强的机理和粗骨料的作用机制.结果表明:随着粗骨料掺量的增加,UHPC-CA的单轴抗拉强度与变形性能均下降;钢纤维掺量增加、长径比增大对UHPC-CA的受拉力学性能有较大的提升作用;钢纤维与基体间具有良好的握裹力,在基体内出现裂缝后,主要依靠握裹作用承受拉应力;粗骨料的掺入削弱了钢纤维空间分布的均匀性,同时引入了薄弱的粗骨料-基体界面过渡区,对UHPC-CA的受拉性能产生了不利的影响.

关键词：超高性能混凝土粗骨料应力-应变关系纤维增强机理

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Relationships between selfreflectiveness and clinical symptoms in individuals during pre-morbid and early clinical stages of psychosis

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General Psychiatry 2022年第3期35卷 163-172页

作者： lihua xu Huiru Cui Yanyan Wei Zhenying Qian Xiaochen Tang Yegang Hu Yingchan Wang Hao Hu Qian Guo Yingying Tang Tianhong Zhang Jijun Wang Shanghai Intelligent Psychological Evaluation and Intervention Engineering Technology Research Center Shanghai Key Laboratory of Psychotic DisordersShanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina Department of Psychiatry Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina Department of Early Psychotic Disorders Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina Center for Excellence in Brain Science and Intelligence Technology(CEBSIT) Chinese Academy of ScienceShanghaiChina Brain Science and Technology Research Center Shanghai Jiao Tong UniversityShanghaiChina

Background Self-reflectiveness,one dimension of cognitive insight,plays a protective role in an individual’s mental state.Both high and low levels of self-reflectiveness have been reported in patients with schizophrenia and individuals at clinical high risk for the illness.Aims This study aimed to explore the relationship patterns between self-reflectiveness and clinical symptoms in individuals during the pre-morbid and early clinical stages of psychosis.Methods A total of 181 subjects,including individuals with attenuated positive symptoms(APS,n=122)and patients with first-episode psychosis(FEP,n=59),completed the Beck Cognitive Insight Scale and were evaluated using the Schedule of Assessment of Insight and Positive and Negative Syndrome Scale.All subjects were classified into three groups according to their level of selfreflectiveness:low level(LSR,n=59),medium level(MSR,n=67)and high level(HSR,n=55).Both linear and nonlinear relationships between self-reflectiveness and clinical symptoms were explored.Results More individuals with APS were classified into the MSR group,while more patients with FEP were classified into the LSR group.The LSR group demonstrated less awareness of illness than the MSR and HSR groups,more stereotyped thinking and poorer impulse control but less anxiety than the MSR group,and lower levels of blunted affect and guilt feelings than the HSR group.The MSR group demonstrated lower stereotyped thinking than the HSR group.Compared to the LSR group,the MSR group had increased selfreflectiveness,improved awareness of illness,decreased stereotyped thinking,and better impulse control,but increased feelings of guilt.The HSR group showed increased stereotyped thinking when compared to the MSR group,but the other variables did not change significantly between these two groups.Overall,self-reflectiveness demonstrated an approximately inverse S-shaped relationship with the awareness of illness,a U-shaped relationship with stereotyped thinking and poor impulse control,and an almost linear relationsh

关键词： clinical symptoms morbid

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Abnormal neural oscillations in clinical high risk for psychosis:a magnetoencephalography method study

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General Psychiatry 2022年第2期35卷 148-153页

作者： Yegang Hu Jun Wu Yujiao Cao Xiaochen Tang Guisen Wu Qian Guo lihua xu Zhenying Qian Yanyan Wei Yingying Tang Chunbo Li Tianhong Zhang Jijun Wang Shanghai Mental Health Center Shanghai Jiao Tong University School of MedicineShanghaiChina

Background Neural oscillations directly reflect the rhythmic changes of brain activities during the resting state or while performing specific tasks.Abnormal neural oscillations have been discovered in patients with schizophrenia.However,there is limited evidence available on abnormal spontaneous neural oscillations in clinical high risk for psychosis(CHR-P).The brain signals recorded by the magnetoencephalography(MEG)technique are not to be disrupted by the skull and scalp.Methods In this study,we applied the MEG technique to record the resting-state neural activities in CHR-P.This was followed by a detailed MEG analysis method including three steps:(1)preprocessing,which was band-pass filtering based on the 0.5-60Hz frequency range,removal of 50Hz power frequency interference,and removal of electrocardiography(ECG)and electrooculography(EOG)artefacts by independent component analysis;(2)time-frequency analysis,a multitaper time-frequency transformation based on the Hanning window,and(3)source localisation.an exact low-resolution brain electromagnetic tomography.The method was verified by comparing aparticipant with CHR-P with a healthy control during the MEG recordings with an eyes-closed resting state.Results Experimental results show that the neural oscillations in CHR-P were significantly abnormal in the theta frequency band(4-7Hz)and the delta frequency band(1-3Hz).Also,relevant brain regions were located in the left occipital lobe and left temporo-occipital junction for the theta band and in the right dorsolateral prefrontal lobe and near orbitofrontal gyrus for the delta band.Conclusions Abnormal neural oscillations based on specific frequency bands and corresponding brain sources may become biomarkers for high-risk groups.Further work will validate these characteristics in CHR-P cohorts.

关键词： steps bands exact

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